We wish to develop and test procedures to measure the mutagenic activity of chemotherapeutic agents used to treat human herpes virus infections. The most effective anti-viral agents against herpes simplex virus infections are nucleoside analogues that exert their selective toxicity because they are converted to nucleotides by the viral enzyme, thymidine kinase. Some of these analogues are known to be mutagenic. The goal of the proposed research is to construct lines of cultured mammalian cells that express the HSV thymidine kinase and by use of these cells determine if anti-herpetic drugs cause well-defined nutritional and drug resistance markers to undergo further mutation. The strategy outlined above is analogous to that described by Ames in which bacteria with defined mutations are used to detect chemical carcinogens.